Clinical Research Directory

Safety and Efficacy Study of Safusidenib in Participants With IDH1-Mutant Glioma Who Discontinued Vorasidenib Treatment Due to Progressive Disease

This study will include up to 40 participants with Grade 2 or Grade 3 IDH1-mutant glioma who have undergone surgery and received vorasidenib as their only treatment, experienced radiographic disease progression on vorasidenib (confirmed by Blinded Independent Central Review \[BICR\] per modified Response Assessment in Neuro-Oncology \[RANO\] 2.0), and are not in need of immediate chemotherapy or radiotherapy.

Novel Indenoisoquinolone CMYC/TOPOISOMERASE 1 Inhibitor (LMP744) in Recurrent Glioblastoma

Background: Glioblastoma is a common brain cancer in adults. Treatment includes surgery, radiation, and chemotherapy. But this cancer can return after treatment and is often fatal. Researchers want to know if a study drug (LMP744) can kill glioblastoma tumor cells. Objective: To test LMP744 in people with glioblastoma. Eligibility: People aged 18 years or older with glioblastoma that returned after treatment. Design: Participants will be screened. They will have a surgery to remove a small sample of tumor tissue (biopsy) from the brain. This will be done under protocol 03-N-0164. They will stay in the clinic for 1 night. They will also have imaging scans and tests of their heart function. Participants will have a central line installed: A flexible tube will be inserted into a vein in the chest. It will be attached to a port under the skin. This port will be used to draw blood and give medicines without having to insert new needles into a vein. LMP744 will be given through the central line for 5 days in a row. Participants will remain in the clinic for this time. Participants will then have a second surgery to remove as much of their tumor as possible. They will remain in the clinic until they recover from the surgery. Then they will recover at home after surgery. Participants will return to the clinic to receive the study drug for 5 days in a row through the central line, once a month for up to 12 months. Blood tests, heart function tests, and periodic imaging scans will be repeated during these visits. Participants will continue to have telehealth visits every 3 months after they stop taking the drug.

Hypofractionation Trial of Re-irradiation in Good Prognosis Recurrent Glioblastoma

Background: Glioblastoma (GBM) is a cancer of the brain. Current survival rates for people with GBM are poor; survival ranges from 5.2 months to 39 months. Most tumors come back within months or years after treatment, and when they do, they are worse: Overall survival drops to less than 10 months. No standard treatment exists for people whose GBM has returned after radiation therapy. Objective: To find a safe schedule for using radiation to treat GBM tumors that returned after initial radiation treatment. Eligibility: People aged 18 years and older with grade 4 GBM that returned after initial radiation treatment. Design: Participants will be screened. They will have a physical exam with blood tests. A sample of tumor tissue may be collected. Participants will undergo re-irradiation planning: They will wear a plastic mask over their head during imaging scans. These scans will pinpoint the exact location of the tumor. This spot will be the target of the radiation treatments. Participants will undergo radiation treatment 4 times per week. Some people will have this treatment for 3 weeks, some for 2 weeks, and some for 1 week. Blood tests and other exams will be repeated at each visit. Participants will complete questionnaires about their physical and mental health. They will answer these questions before starting radiation treatment; once a week during treatment; and at intervals for up to 3 years after treatment ends. Participants will have follow-up visits 1 month after treatment and then every 2 months for 6 months. Follow-up clinic visits will continue up to 3 years. Follow-ups by phone or email will continue an additional 2 years.

AI-Assisted MRI Molecular Subtyping in Pediatric Brain Tumors

This multicenter observational cohort study aims to develop and validate an artificial intelligence (AI)-assisted diagnostic system for preoperative molecular subtyping of pediatric brain tumors using routine magnetic resonance imaging (MRI). The study will include seven major pediatric brain tumor categories: glioma, medulloblastoma, ependymoma, atypical teratoid/rhabdoid tumor (AT/RT), intracranial germ cell tumors, craniopharyngioma, and choroid plexus tumors. The study includes a retrospective cohort for model development and internal/external validation, and a prospective cohort for further validation. Retrospective data will be collected from pediatric patients who underwent first surgical treatment between January 1, 2020 and December 31, 2025. Prospective enrollment will begin on July 15, 2026, with an anticipated sample size of 150 participants. The AI system will analyze preoperative MRI sequences, including T1-weighted, contrast-enhanced T1-weighted, T2-weighted, and FLAIR images, to predict key molecular markers and integrated diagnostic categories. The primary objective is to evaluate the diagnostic performance of the AI system for prespecified molecular prediction tasks using postoperative histopathology and molecular testing as the reference standard. Secondary objectives include assessing agreement with integrated diagnosis, comparing performance against blinded radiologists, and exploring prognostic associations of AI-predicted subgroups.

Clinical Benefit of 18F-FET in Glioma.

This Phase II clinical trial, sponsored by \*\*Primo Biotechnology Co., Ltd.\*\*, evaluates the clinical benefit of \*\*$\^{18}$F-FET PET/CT\*\* in diagnosing glioma. The study aims to compare the diagnostic performance of $\^{18}$F-FET PET imaging against traditional brain MRI, using surgical histopathology as the gold standard for verification. \*\*Study Design and Participants\*\* This is a single-center, open-label, non-randomized trial conducted in Taiwan. The study will enroll a total of \*\*36 participants\*\*, consisting of 6 healthy volunteers (to assess biodistribution and dosimetry) and 30 patients with suspected primary gliomas scheduled for surgery. \*\*Methodology\*\* The test drug, $\^{18}$F-FET, is a radiopharmaceutical that targets large neutral amino acid transporters (LAT). It is administered via intravenous injection at a dosage of 3MBq/kgw. * \*\*Volunteers\*\* undergo PET/CT scans immediately and every 20 minutes for 90 minutes. * \*\*Patients\*\* receive a static PET scan 40-50 minutes post-injection. \*\*Endpoints and Safety\*\* * \*\*Primary Endpoint:\*\* Diagnostic sensitivity compared to MRI. * \*\*Secondary Endpoints:\*\* Specificity, PPV, NPV, tumor-to-background ratios (TBR), and safety (adverse events/vital signs). * \*\*Radiation Safety:\*\* The total estimated radiation exposure is \*\*7.63 mSv\*\*, which is well below the international safety threshold of 100 mSv. \*\*Conclusion\*\* The trial seeks to establish $\^{18}$F-FET PET/CT as a safe and effective diagnostic tool for the pre-surgical assessment of gliomas, potentially providing higher sensitivity and more accurate lesion detection than conventional MRI in Asian cancer patients.

Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

This phase II MATCH screening and multi-sub-trial studies how well treatment that is directed by genetic testing works in patients with solid tumors, lymphomas, or multiple myelomas that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and does not respond to treatment (refractory). Patients must have progressed following at least one line of standard treatment or for which no agreed upon treatment approach exists. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic abnormalities (such as mutations, amplifications, or translocations) may benefit more from treatment which targets their tumor's particular genetic abnormality. Identifying these genetic abnormalities first may help doctors plan better treatment for patients with solid tumors, lymphomas, or multiple myeloma.

A Study of HF1K16 Combined With Bevacizumab in Patients With Recurrent or Progressive Glioma

The primary purpose of this Phase II study is to evaluate the preliminary anti-tumor efficacy of HF1K16 in combination with Bevacizumab in patients with recurrent or progressive glioma. The study also evaluates the safety and tolerability of the combination therapy.

Study of Silevertinib With Temozolomide for the Treatment of Newly Diagnosed GBM With Unmethylated MGMT and EGFRvIII

The purpose of this study is to see if combining silevertinib with temozolomide after surgery and radiotherapy helps treat newly diagnosed glioblastoma (GBM) better than using temozolomide alone in the maintenance setting. Specifically, this study is being done to find answers to the following questions: * How much of the study drugs (silevertinib combined with temozolomide) should be given to participants with GBM? * What are the side effects participants have when taking the study drug (silevertinib combined with temozolomide)? * Can the study drug (silevertinib combined with temozolomide) help participants with GBM live longer without disease progression compared to treatment with temozolomide alone?

A Study to Learn About the Study Medicine Called PF-07799544 as Monotherapy or in Combination in People With Advanced Solid Tumors

The purpose of this clinical trial is to learn the safety and effects of the study medicine (PF-07799544) alone or in combination as a potential cancer treatment for adults with advanced solid tumors. The study will be conducted in two parts: PF-07799544 as a single agent (Phase 1a) and PF-07799544 in combination with another study medicine called PF-07799933 (Phase 1b). Phase 1a is no longer open for enrollment. In Phase1b (noted as "this study"), we are seeking participants who have: * a solid tumor which is metastatic or recurrent (excluding colorectal cancer) * tumor with the mutation (abnormal gene) called "BRAF V600" * received required prior treatment for cancer per cohort assigned. All participants in this study will receive both study medicines. Both study medicines are tablets that are taken by mouth at home twice a day. Participants will receive study medicines until their cancer is no longer responding, unacceptable side effects, or 2 years. Participants may continue to receive study therapy beyond 2 years. We will examine the experiences of people receiving the study medicines. This will help us determine if the study medicines are safe and effective.

A Study to Learn About the Study Medicine Called PF-07799933 in People With Advanced Solid Tumors With BRAF Alterations.

The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called PF-07799933) administered as a single agent and in combination with other study medicines in people with solid tumors. This study is seeking participants who have an advanced solid tumor with a certain type of abnormal gene called "BRAF" and available treatments are no longer effective in controlling their cancer. All participants in this study will receive PF-07799933. PF-07799933 comes as a tablet to take by mouth, 2 times a day. Depending on the part of the study, participants may also receive another study medicine: * People with melanoma or other solid tumors may also receive binimetinib. Binimetinib comes as a tablet to take by mouth, 2 times a day. * People with colorectal cancer may also receive cetuximab or cetuximab and mFOLFOX6 (Chemotherapy regimen). Cetuximab will be given weekly (or every two weeks) in the clinic as a shot given in the vein or port (intravenous, IV). Participants may receive the study medicines for about 2 years. The study team will monitor how each participant is doing with the study treatment during regular visits at the study clinic.

MRS of Glioma Genomics

In France, about 5000 new people with a primary malignant brain tumor are diagnosed each year. The most common primary tumors are gliomas, originating from glial cells (astrocytomas and oligodendrogliomas). Low-grade gliomas are mildly aggressive, but they often evolve into a more malignant form. Mutations in the genes encoding isocitrate dehydrogenase (IDH) are found in about 80% of low-grade gliomas and are associated with a favorable prognosis. Remarkably, IDH-mutated gliomas are characterized by a specific cellular metabolism causing the accumulation of D-2-hydroxyglutarate (2HG) in tumor cells. 2HG can be detected in vivo using 1H magnetic resonance spectroscopy (MRS) and is recognized as a unique, noninvasive biomarker of IDH-mutated gliomas. Noninvasive detection of IDH mutations via 2HG MRS represents a crucial step for decision-making and patient care. A subset of IDH-mutated tumors also presents a complete deletion of 1p and 19q chromosome arms (1p/19q codeletion). The 1p/19q codeletion is specifically linked to the oligodendroglial histologic subtype and it has been associated with a better patient outcome. However, the biological effects of this genetic alteration are still unclear and in vivo markers are lacking. Recently, we reported the first in vivo detection of the cystathionine molecule in human brain gliomas using MRS and explored the association between cystathionine accumulation and 1p/19q codeletion in gliomas. In this project, the investigation team will combine cutting edge MRI and MRS techniques for metabolic and microstructural characterization of brain tumors with the aim of providing novel reliable noninvasive biomarkers of tumor genetic subtypes. These methods will enable noninvasive identification of IDH-mutated gliomas and, potentially, 1p/19q codeleted gliomas. In addition, the researchers will investigate the utility of 2HG, cystathionine and MRI microstructural markers to monitor tumor response to anti-cancer treatments and tumor progression. The outputs of this project, altogether, may open new avenues to a better understanding of the pathophysiological mechanisms of oncogenesis and the design of new treatments for gliomas.

Studying the Biology of IDH-mutant Gliomas Via Longitudinal Observation of 2-hydroxyglutarate (2-HG) Using MR Spectroscopy

Background: Glioma is a type of brain cancer. Some of these tumors have gene mutations. These mutations can cause a substance called 2-HG to build up in the brain. This makes the tumors more aggressive. Researchers want to better understand 2-HG buildup in the brain. They hope this can help them design better ways to test for gliomas. Objective: To monitor the level of 2-HG in the brains of people with gliomas that have mutations in the IDH1 or IDH2 genes. Eligibility: People ages 18 and older with gliomas with mutations in the IDH1 or IDH2 genes Design: Participants will be screened with: Medical and cancer history Physical exam Reviews of their symptoms and ability to perform normal activities Blood and urine tests MRI scan Samples of their tumor from a past surgery Documentation of their diagnosis and mutation status Participants will have an initial evaluation. This will include repeats of screening tests. It will also include: Neurological exam MRS and MRI scans of the brain: Participants will lie on a table that slides into a metal cylinder. A coil or soft padding will be placed around their head. They will have a contrast agent injected into a vein. Pictures will be taken of the brain. Participants will have follow-up visits every 2-6 month for the rest of their life. Visits will include scans.

Study of LY3410738 Administered to Patients With Advanced Solid Tumors With IDH1 or IDH2 Mutations

This is an open-label, multicenter Phase 1 study to evaluate safety, tolerability and preliminary efficacy of oral LY3410738 in patients with isocitrate dehydrogenase 1 (IDH1) arginine 132 (R132)-mutant advanced solid tumors, including but not limited to cholangiocarcinoma, chondrosarcoma, and glioma or isocitrate dehydrogenase 2 (IDH2) arginine 140 (R140) or arginine 172 (R172) mutant cholangiocarcinoma.

3D-ASL and TDD-MRI for True Progression and Pseudoprogression After Glioma Surgery

Background: Differentiating true progression (TP) from pseudoprogression (PsP) after glioma surgery remains a major clinical challenge because conventional magnetic resonance imaging (MRI) often cannot reliably distinguish these conditions. Objective: This prospective observational diagnostic accuracy study aims to evaluate the value of multiparametric imaging based on three-dimensional arterial spin labeling (3D-ASL) combined with time-dependent diffusion MRI (TDD-MRI) for differentiating TP from PsP in postoperative glioma patients. Methods: Consecutive adult patients with suspected tumor progression after glioma surgery will undergo routine MRI, 3D-ASL, and TDD-MRI examinations. Quantitative perfusion and diffusion parameters will be extracted, and a combined imaging model will be developed and evaluated. Final diagnosis will be established according to pathological findings when available or by longitudinal clinical and imaging follow-up based on the Response Assessment in Neuro-Oncology (RANO) criteria. Expected Outcomes: The primary outcome is the diagnostic performance of the combined imaging model, assessed by the area under the receiver operating characteristic curve (AUC). The study is expected to provide a noninvasive imaging strategy for distinguishing TP from PsP and to support clinical decision-making during postoperative follow-up.

Medication Combinations of Dasatinib, Quercetin, Fisetin, Temozolomide, LMP744, and Autologous TLPO Vaccine for the Treatment of Previously Treated Glioma With Residual Disease

This early phase I trial tests the safety, side effects and how well medication combinations of dasatinib, quercetin, fisetin, temozolomide, LMP744, and autologous tumor lysate particle only (TLPO) vaccine work in treating patients with glioma for which the patient has received treatment in the past (previously treated) and for tumor cells that remain after attempts to treat the tumor have been made (residual disease). Dasatinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply, which may help keep tumor cells from growing. Quercetin and fisetin are compounds found in plants. They have antioxidant and anti-inflammatory properties and help remove senescent cells, older or damaged cells that have stopped dividing but don't die off as they should and build up in tissues over time. Senescent cells may cause inflammation or damage to nearby healthy cells. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill tumor cells and slow down or stop tumor growth. LMP744 works by interfering with a protein that tumor cells use to copy and repair their DNA. By blocking this repair process, the drug causes DNA damage so that tumor cells cannot survive. The autologous TLPO vaccine is made using material from a patient's own tumor. It delivers the tumor material to immune cells so they can learn to recognize and attack the cancer. Giving medication combinations of dasatinib, quercetin, fisetin, temozolomide, LMP744, and autologous TLPO vaccine may be safe, tolerable and/or effective in treating patients with previously treated glioma with residual disease.

Proton Beam or Intensity-Modulated Radiation Therapy in Preserving Brain Function in Patients With IDH Mutant Grade II or III Glioma

This randomized phase II clinical trial studies the side effects and how well proton beam or intensity-modulated radiation therapy works in preserving brain function in patients with IDH mutant grade II or III glioma. Proton beam radiation therapy uses tiny charged particles to deliver radiation directly to the tumor and may cause less damage to normal tissue. Intensity-modulated or photon beam radiation therapy uses high-energy x-ray beams shaped to treat the tumor and may also cause less damage to normal tissue. It is not yet known if proton beam radiation therapy is more effective than photon-based beam intensity-modulated radiation therapy in treating patients with glioma.

SIGMA (Safusidenib in IDH1 Mutant Glioma Maintenance)

This is a 3-part study. The purpose of Part 1 of the study is to evaluate the efficacy, safety, and pharmacokinetic (PK) characteristics of safusidenib in participants with recurrent/progressive IDH1-mutant World Health Organization (WHO) Grade 2 or Grade 3 glioma. The purpose of Part 2 will be to evaluate the efficacy of maintenance safusidenib treatment versus placebo in IDH1-mutant Grade 2 or Grade 3 astrocytoma with high-risk features or IDH1-mutant Grade 4 astrocytoma, following standard-of-care radiation or chemoradiation and adjuvant temozolomide. Part 2 will be randomized, double-blind, and placebo-controlled. The purpose of Part 3 will be to evaluate the efficacy of safusidenib in participants with residual or recurrent IDH1-mutant Grade 3 oligodendroglioma who have received surgery as their only treatment. Part 3 will be an open-label single-arm cohort and will enroll participants concurrently with Part 2.

Window Trial of Fluorescently Labeled Nivolumab-IRDye800 (Nivo800) in High Grade Glioma (HGG)

High-grade gliomas (HGGs) are among the most aggressive and treatment-resistant brain tumors. Immunotherapy with checkpoint inhibitors like nivolumab has shown promise, but its efficacy remains variable and poorly understood in this patient population. This clinical trial investigates a novel imaging-enabled formulation of nivolumab-IRDye800 (nivo800) which incorporates a near-infrared (NIR) fluorescent dye to enable real-time visualization of drug distribution within tumor tissue.

FIH Clinical Investigation of Graphene Electrodes for Brain Mapping

The goal of this clinical investigation of a medical device is to test the safety of graphene based electrodes when used during surgery for resection of brain tumors. The main questions that it aims to answer are: * To understand the safety of the Graphene Cortical Interface when used during brain tumor surgery (primary objective); * To assess the quality of the brain signals recorded with the Graphene Cortical Interface, their ability to stimulate the brain, how stable their function is over the duration of an operation, and their suitability for use in the operating theatre (secondary objectives). Participants will undergo tumor surgery as usual with the study electrodes being tested alongside a standard monitoring system. If they are awake for part of their surgery they may be asked to complete specific tasks such as naming objects from a list modified for the study, to evaluate the capability to decode brain signals (exploratory objective). They will be monitored subsequently for any complications including undergoing an additional MRI scan 6 weeks after their surgery.

GliomaAI-Astro4: MRI-Based Detection of IDH Mutant Astrocytoma Grade 4

The goal of this observational study is to learn whether an artificial intelligence system called GliomaAI-Astro4 can help detect a specific molecular type of brain tumour called IDH mutant Astrocytoma Grade 4 using routine MRI scans. The study uses previously collected and fully anonymised MRI data from 1,372 patients from 13 institutions in the Cancer Imaging Archive (TCIA). The main questions it aims to answer are: * How accurately can GliomaAI-Astro4 identify IDH mutant Astrocytoma Grade 4 from MRI scans? * How well does the system perform across data from different hospitals and patient groups? Researchers will use existing MRI scans and clinical information to train and test the AI system. No new scans, treatments, or hospital visits are required for participants, and all data used is fully anonymised and obtained from an existing research database. Participants will not be asked to do anything, as this study only uses previously collected imaging data.

GliomaAI-GBM: MRI-Based Detection of IDH Wildtype Glioblastoma

The goal of this observational study is to learn whether an artificial intelligence system called GliomaAI-GBM can help detect a specific molecular type of brain tumour called IDH wildtype glioblastoma using routine MRI scans. The study uses previously collected and fully anonymised MRI data from 1,372 patients from 13 institutions in the Cancer Imaging Archive (TCIA). The main questions it aims to answer are: * How accurately can GliomaAI-GBM identify IDH wildtype glioblastoma from MRI scans? * How well does the system perform across data from different hospitals and patient groups? Researchers will use existing MRI scans and clinical information to train and test the AI system. No new scans, treatments, or hospital visits are required for participants, and all data used is fully anonymised and obtained from an existing research database. Participants will not be asked to do anything, as this study only uses previously collected imaging data.

GliomaAI-Astro23: MRI-Based Detection of IDH Mutant Astrocytoma (Grade 2 and 3)

The goal of this observational study is to learn whether an artificial intelligence system called GliomaAI-Astro23 can help detect a specific molecular type of brain tumour called IDH mutant Astrocytoma (grade 2 and 3) using routine MRI scans. The study uses previously collected and fully anonymised MRI data from 1,372 patients from 13 institutions in the Cancer Imaging Archive (TCIA). The main questions it aims to answer are: * How accurately can GliomaAI-Astro23 identify IDH mutant Astrocytoma (grade 2 and 3) from MRI scans? * How well does the system perform across data from different hospitals and patient groups? Researchers will use existing MRI scans and clinical information to train and test the AI system. No new scans, treatments, or hospital visits are required for participants, and all data used is fully anonymised and obtained from an existing research database. Participants will not be asked to do anything, as this study only uses previously collected imaging data.

Glioma Developmental and HyperActive Ras Tumor (DHART) Board

This study will collect medical records, scan results, and complete surveys to create a registry about people with a neurofibromatosis type 1-associated brain tumor (NF1-associated glioma). A registry is a collection of health information about individuals, and it is usually focused on a specific diagnosis or condition. This registry study will help the researchers learn more about the diagnosis, treatment, and quality of life of people with NF1-associated glioma. The researchers want to understand what happens as a result of different treatments for NF1-associated glioma and how these treatments and the disease itself affect people's lives over a period of time. Information collected during this study could affect how doctors diagnose, test, and treat NF1-associated glioma, and the study could help future patients with this type of cancer.

GliomaAI-Oligo: MRI-Based Detection of IDH Mutant Oligodendroglioma

The goal of this observational study is to learn whether an artificial intelligence system called GliomaAI-Oligo can help detect a specific molecular type of brain tumour called Oligodendroglioma using routine MRI scans. The study uses previously collected and fully anonymised MRI data from 1,372 patients from 13 institutions in the Cancer Imaging Archive (TCIA). The main questions it aims to answer are: * How accurately can GliomaAI-Oligo identify Oligodendroglioma from MRI scans? * How well does the system perform across data from different hospitals and patient groups? Researchers will use existing MRI scans and clinical information to train and test the AI system. No new scans, treatments, or hospital visits are required for participants, and all data used is fully anonymised and obtained from an existing research database. Participants will not be asked to do anything, as this study only uses previously collected imaging data.